Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics

Janin, Maxime; Dávalos, Verónica; Esteller, Manel

doi:10.1007/s10555-023-10120-3

Cited by 4 publications

(1 citation statement)

References 395 publications

(176 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epigenetic modifications mediated by methyltransferases, demethylases, acetyltransferases, and deacetylases affect the metastatic process of many cancers, including breast cancer ( 44 – 47 ). The effect of the tumour micro-environment on the epigenetics and thus metastatic ability of primary lung cancers was recently reviewed in ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model

Herst,

Carson,

Lewthwaite

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

BackgroundFast adaptation of glycolytic and mitochondrial energy pathways to changes in the tumour microenvironment is a hallmark of cancer. Purely glycolytic ρ0 tumour cells do not form primary tumours unless they acquire healthy mitochondria from their micro-environment. Here we explored the effects of severely compromised respiration on the metastatic capability of 4T1 mouse breast cancer cells.Methods4T1 cell lines with different levels of respiratory capacity were generated; the Seahorse extracellular flux analyser was used to evaluate oxygen consumption rates, fluorescent confocal microscopy to assess the number of SYBR gold-stained mitochondrial DNA nucleoids, and the presence of the ATP5B protein in the cytoplasm and fluorescent in situ nuclear hybridization was used to establish ploidy. MinION nanopore RNA sequence analysis was used to compare mitochondrial DNA transcription between cell lines. Orthotopic injection was used to determine the ability of cells to metastasize to the lungs of female Balb/c mice.ResultsOXPHOS-deficient ATP5B-KO3.1 cells did not generate primary tumours. Severely OXPHOS compromised ρ0D5 cells generated both primary tumours and lung metastases. Cells generated from lung metastasis of both OXPHOS-competent and OXPHOS-compromised cells formed primary tumours but no metastases when re-injected into mice. OXPHOS-compromised cells significantly increased their mtDNA content, but this did not result in increased OXPHOS capacity, which was not due to decreased mtDNA transcription. Gene set enrichment analysis suggests that certain cells derived from lung metastases downregulate their epithelial-to-mesenchymal related pathways.ConclusionIn summary, OXPHOS is required for tumorigenesis in this orthotopic mouse breast cancer model but even very low levels of OXPHOS are sufficient to generate both primary tumours and lung metastases.

show abstract

Section: Discussionmentioning

confidence: 99%

Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model

Herst,

Carson,

Lewthwaite

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

Role of RNA modifications in cancer metastasis

Malka-Tunitsky,

Sas-Chen

2024

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

The Epigenetic Hallmarks of Cancer

Esteller,

Dawson,

Kadoch

et al. 2024

Cancer Discovery

View full text Add to dashboard Cite

Cancer is a complex disease in which several molecular and cellular pathways converge to foster the tumoral phenotype. Notably, in the latest iteration of the cancer hallmarks, “nonmutational epigenetic reprogramming” was newly added. However, epigenetics, much like genetics, is a broad scientific area that deserves further attention due to its multiple roles in cancer initiation, progression, and adaptive nature. Herein, we present a detailed examination of the epigenetic hallmarks affected in human cancer, elucidating the pathways and genes involved, and dissecting the disrupted landscapes for DNA methylation, histone modifications, and chromatin architecture that define the disease. Significance: Cancer is a disease characterized by constant evolution, spanning from its initial premalignant stages to the advanced invasive and disseminated stages. It is a pathology that is able to adapt and survive amidst hostile cellular microenvironments and diverse treatments implemented by medical professionals. The more fixed setup of the genetic structure cannot fully provide transformed cells with the tools to survive but the rapid and plastic nature of epigenetic changes is ready for the task. This review summarizes the epigenetic hallmarks that define the ecological success of cancer cells in our bodies.

show abstract

Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics

Cited by 4 publications

References 395 publications

Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model

Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model

Role of RNA modifications in cancer metastasis

The Epigenetic Hallmarks of Cancer

Contact Info

Product

Resources

About